DESCRIPTION (Principal Investigator's Abstract): This proposal contains a group of descriptive and metabolic studies to explore a new surgical procedure for the treatment of obesity. This procedure has been previously studied in rats and consists of a subdiaphragmatic truncal vagotomy and ileal transposition (VIT). VIT appeared in rats to be more effective, with few of the complications usually associated with intestinal bypass surgery. The purpose of this application is to assess the effectiveness of VIT in a larger animal model which more resembles that of humans as a preliminary for human studies. Seven experiments are proposed. The animal model will consist of pigs, both standard size Yorkshire pigs for the long term studies and mini pigs for some of the metabolic studies. The first is a safety and efficacy study comparing eight animals receiving VIT and eight who are sham operated. Body weight and routine blood tests for general health will be performed and animals will be monitored over a four year period. After this, they will be sacrificed and organs will be examined both grossly and histologically. The second experiment will examine changes in the sympathetic nervous system activity during fasting and feeding in VIT and sham operated pigs. Norepinephrine turnover study will performed before and after a meal. In the third experiment, gastric emptying and intestinal motility will be examined in the VIT and sham operated pigs. Intestinal motility will be evaluated by barium, and gastric capacity through the ingestion of radio-opaque pellets. In the fourth experiment VIT or sham operated mini pigs will be used to compare energy expenditure and energy balance on both high fat and high carbohydrate diets. After one month on the two defined diets, and energy balance study will be performed along with indirect calorimetry, norepinephrine turnover study and an euglycemic clamp study. In the fifth experiment, the "defense" of body weight will be tested by overfeeding and underfeeding through the use of gastric infusion of a liquid formula diet. Norepinephrine turnover rates, hormone substrate measurements and clamps will be performed before and after the weight gain and weight loss studies. In the sixth experiment, "defense" of body weight will be examined through pair feeding. Sham and VIT operated mini pigs will be pair fed for a period of three months to see if VIT operated animals weight less consuming the same amount of food as their sham operated controls, and then an apparent weight loss experiment will be conducted where food intake will be cut by 50 percent. The last experiment explores a possible humoral factor present in the plasma of VIT pigs. This will be obtained by plasmapheresis in the VIT pigs and administered either to assess acute effects on food intake or to assess chronic effects on food intake and body weight.